Pharmaceutical composition containing palbociclib and letrozole

Abstract

A pharmaceutical composition containing palbociclib tosylate and letrozole, in which palbociclib tosylate and letrozole are in one dosage unit, and the particles of the active ingredient palbociclib tosylate and letrozole are not separated from each other, and the production of the pharmaceutical preparation, the granule containing palbociclib tosylate and letrozole, the use of the pharmaceutical preparation and special blister packaging that facilitates the use of a specific dosage regimen.

1 - 16 . (canceled) 
     
     
         17 . A method of treatment of cancer,
 or   for the treatment of breast cancer,   or   for the treatment of cancer that is locally advanced or metastatic and the cancer cells have receptors of hormones on their surface and the cancer cells do not produce abnormally large amounts of A receptor called HER2   comprising administering to a subject in need thereof a pharmaceutical composition comprising the 4-toluenesulfonic acid salt of palbociclib and letrozole,   and optionally, periodically administering alternately with letrozole;   optionally wherein unit doses containing palbociclib 4-tosylate and letrozole are administered during the treatment for 21 days, and then letrozole mono composition is administered for 22-28 days, and then optionally, this 28-day treatment cycle is repeated;   optionally wherein the amount of palbociclib tosylate in the unit doses containing palbociclib 4-tosylate and letrozole corresponds to 75 mg, 100 mg or 125 mg palbociclib base and letrozole content is 2.5 mg, and in mono unit doses containing letrozole, the amount of letrozole is 2.5 mg.   
     
     
         18 . A method of treatment of HR-positive, HER-negative breast cancer, comprising
 administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising the 4-toluenesulfonic acid salt of palbociclib and letrozole, optionally wherein the administration of the composition is periodically replaced/supplemented with a mono composition containing letrozole alone, in which unit doses containing palbociclib 4-tosylate and letrozole are administered for 21 days, and then a mono composition containing letrozole is administered for 7 days, and then, optionally, this dosage regimen is repeated.   
     
     
         19 . The method of  claim 17 , which is for the treatment of breast cancer. 
     
     
         20 . The method of  claim 17 , which is for the treatment of cancer that is locally advanced or metastatic and the cancer cells have receptors of hormones on their surface and the cancer cells do not produce abnormally large amounts of A receptor called HER2. 
     
     
         21 . The method of  claim 20 , wherein the cancer cells are HR-positive. 
     
     
         22 . The method of  claim 17 , comprising administering to a subject in need thereof a pharmaceutical composition comprising the 4-toluenesulfonic acid salt of palbociclib and letrozole, and periodically administering alternately with letrozole. 
     
     
         23 . The method of  claim 17 , wherein unit doses containing palbociclib 4-tosylate and letrozole are administered during the treatment for 21 days, and then letrozole mono composition is administered for 22-28 days, and then optionally, this 28-day treatment cycle is repeated. 
     
     
         24 . The method of  claim 17 , wherein the amount of palbociclib tosylate in the unit doses containing palbociclib 4-tosylate and letrozole corresponds to 75 mg, 100 mg or 125 mg palbociclib base and letrozole content is 2.5 mg, and in mono unit doses containing letrozole, the amount of letrozole is 2.5 mg. 
     
     
         25 . The method of  claim 17 , wherein in the pharmaceutical composition the 4-toluenesulfonic acid salt of Palbociclib and letrozole are not isolated from each other, and/or the 4-toluenesulfonic acid salt of Palbociclib and letrozole are homogenized in the composition. 
     
     
         26 . The method of  claim 17 , wherein in the pharmaceutical composition the the palbociclib tosylate (1:1) is a salt form, and wherein the characteristic X-ray powder diffraction peaks of the 4-toluenesulfonic acid (1:1) salt of palbociclib are as follows: Cu Kα (1.1541874 Å) (±0.2° 2θ): 5.18; 10.25; 13.45; 16.08; 21.56. 
     
     
         27 . The method of  claim 17 , wherein the pharmaceutical composition is in the form of granules comprising the 4-toluenesulfonic acid salt of palbociclib and letrozole. 
     
     
         28 . The method of  claim 18 , wherein the administration of the composition is periodically replaced/supplemented with a mono composition containing letrozole alone, in which unit doses containing palbociclib 4-tosylate and letrozole are administered for 21 days, and then a mono composition containing letrozole is administered for 7 days, and then, optionally, this dosage regimen is repeated. 
     
     
         29 . The method of  claim 18 , wherein in the pharmaceutical composition the 4-toluenesulfonic acid salt of Palbociclib and letrozole are not isolated from each other, and/or the 4-toluenesulfonic acid salt of Palbociclib and letrozole are homogenized in the composition. 
     
     
         30 . The method of  claim 18 , wherein in the pharmaceutical composition the the palbociclib tosylate (1:1) is a salt form, and wherein the characteristic X-ray powder diffraction peaks of the 4-toluenesulfonic acid (1:1) salt of palbociclib are as follows: Cu Kα (1.1541874 Å) (±0.2° 2θ): 5.18; 10.25; 13.45; 16.08; 21.56. 
     
     
         31 . The method of  claim 18 , wherein the pharmaceutical composition is in the form of granules comprising the 4-toluenesulfonic acid salt of palbociclib and letrozole.